The Unconscious Baby Flashcards
What are the probable causes of tachypnoea?
- Sepsis even if there is hypothermia
- Cardiovascular diseases such as cyanotic congenital heart disease
- Respiratory disease such as croup, pneumothorax and asthma
- Pain
- Metabolic acidosis causing compensatory tachypnoea
- Raised ammonia which acts as a respiratory stimulant causing tachypnoea
What are inborn errors of metabolism?
Inborn errors of metabolism (IEMs) comprise a group of disorders in which a single gene defect causes a clinically significant block in a metabolic pathway resulting in either accumulation of substrate behind the block or deficiency of the product.
IEMs are defined by:
o Their clinical features.
o Specific enzyme affected
o Their pattern of inheritance
Epidemiology of IEMs
A much higher incidence of 1 in 784 live births has been reported from the West Midlands in the UK.
This is attributed to the effect of ethnicity and consanguinity in the local population.
What is the presentation of IEMs?
• Most metabolic disorders present early in life although milder forms may remain undetected until adulthood.
Various presentations are recognised:
• A neonate or infant presenting with acute metabolic encephalopathy. The initial finding is usually poor feeding and lethargy as in any sick infant and the initial diagnosis is often sepsis. However, in the absence of risk factors for sepsis and poor response to treatment, metabolic disorder needs to be considered. Lethargy can progress to coma and other signs of CNS dysfunction such as abnormal tone or seizures may occur.
- Persistent vomiting in infancy with no clear explanation should raise suspicion of IEM, possibly a defect of protein metabolism.
- Presence of severe metabolic acidosis with increased anion gap should arouse suspicion of an IEM.
- Hypoglycaemia and its associated symptoms such as lethargy or seizures may be a presenting feature in disorders of carbohydrate metabolism or fatty oxidation.
- Jaundice or other evidence of liver dysfunction can be a presenting feature of IEMs such as galactosaemia and glycogen storage disorders.
- Hepatomegaly in the neonatal period or infancy may be a presenting feature of storage disease.
- Coarse facial features along with hepatosplenomegaly and skeletal abnormalities are typical of mucopolysaccharidosis.
- A diagnosis of IEM should also be considered in children with cerebral palsy or developmental delay.
- Abnormal body or urine odour - often noted by mothers or nurses - is an important feature of many IEMs.
IEMs may be an unrecognised cause of intellectual disability in adults.
• IEMs can also present with acidosis or renal stones.
What is PKU?
o Phenylalanine - common disorder causing phenylketonuria (PKU):
- An autosomal recessive disorder because of deficiency of enzyme phenylalanine hydroxylase.
- This results in severe progressive intellectual disability, if untreated by diet.
- Newborn screening for PKU has been performed by heel prick since 1969.
- A low phenylalanine diet is required.
- Strict compliance to the diet is necessary to reduce or to prevent intellectual disability.
What are the defects in metabolism of amino acids?
PKU
o Tyrosine - tyrosinaemia, alkaptouria and albinism.
o Methionine - homocystinuria and hypermethioninaemia.
o Cystine - cystinuria and cystinosis and sulfite oxidase deficiency.
o Tryptophan - Hartnup’s disorder.
o Leucine, isoleucine and valine - maple syrup urine disease (MSUD)
o Glycine - nonketotic hyperglycinaemia, or glycine encephalopathy
o Urea cycle and hyperammonaemia
o Lysine - glutaric aciduria type 1
o Aspartic acid - Canavan’s disease
What is MSUD?
leucine, isoleucine and valine - maple syrup urine disease (MSUD):
- This is a rare disorder due to deficiency of the enzyme branch chain alpha ketoacid dehydrogenase.
- Affected infants are normal at birth, developing poor feeding and vomiting in the first week of life; lethargy and coma may develop in a few days.
- Physical examination shows increased tone and muscular rigidity with opisthotonus which can often lead to a wrong diagnosis of sepsis with meningitis.
- Diagnosis is often suspected because of the peculiar odour of maple syrup found in urine and sweat.
- If left untreated, life-threatening neurological damage may result.
- Treatment includes a special diet low in branched chain amino acids.
- Strict compliance is necessary to prevent neurological damage.
What is nonketotic hyperglycinaemia?
It is caused by deficiency of the glycine cleavage multi-enzyme system.
Four forms have been identified including neonatal, infantile, late-onset and transient.
The neonatal form is the most common and most severe, with babies becoming very unwell in the first few days of life. Poor feeding, lethargy and hypotonia proceeds to coma and seizures with many babies dying and survivors left with profound psychomotor impairment.
What are urea cycle disorders?
Urea cycle and hyperammonaemia:
Catabolism of amino acids results in production of free ammonia which is very toxic to the CNS. The ammonia is detoxified to urea.
Five enzymes are involved in the synthesis of urea and deficiency of any of the individual enzymes can cause hyperammonaemia.
In neonates, symptoms of poor feeding, vomiting, lethargy progressing to coma and convulsions develop within days of starting feeding.
Clinical features of hyperammonaemia in older infants and children are vomiting and neurologic abnormalities such as ataxia, confusion, agitation and irritability. Coma can develop.
Respiratory alkalosis due to ammonia acting as a respiratory stimulant.
What is glutaric aciduria type 1?
Affected infants may have normal development up to 2 years of age.
Macrocephaly is common.
Symptoms of hypotonia, choreoathetosis, seizures and generalised rigidity may develop suddenly after a minor infection.
What is Canavan’s disease?
This is an autosomal recessive condition characterised by spongy degeneration of white matter of the brain, leading to a severe form of leukodystrophy.
Infants are usually normal until 3-6 months of age when they start developing progressive macrocephaly, hypotonia and developmental delay. Hypertonia, stiffness and contractures develop, as are seen in cerebral palsy.
Seizures and optic atrophy develop and most die in the first decade of life.
What are the defects in the metabolism of lipids?
MCAD VLCFAs Hyperlipoproteinaemias Lysosomal storage disorders Mucolipidoses
What is MCAD?
Disorders of mitochondrial fatty acid beta-oxidation (particularly medium chain acetyl-CoA dehydrogenase (MCAD) deficiency now part of the newborn screening programme).
Mitochondrial beta-oxidation of fatty acids is an essential energy-producing pathway which ensures energy production during periods of starvation or low calorie intake as would happen during any illness.
What is VLCFAs?
Disorders of very long chain fatty acids (VLCFAs), which include disorders because of failure to form or maintain the peroxisome (eg, Zellweger’s syndrome) or because of a defect in the function of a single peroxisomal enzyme (eg, adrenoleukodystrophy (ALD)):
- Leukodystrophies cause damage to the myelin sheath.
- People with ALD accumulate high levels of saturated VLCFAs in the brain and adrenal cortex.
- The loss of myelin and the progressive dysfunction of the adrenal gland are the primary characteristics of ALD. Treatment with adrenal hormones can be lifesaving.
- There is evidence that a mixture of oleic acid and erucic acid, ‘Lorenzo’s Oil’, can reduce or delay the appearance of symptoms when given to boys with X-linked ALD.
- Bone marrow transplants may provide long-term benefit to boys who have early evidence of X-linked ALD; however, the procedure carries risks and is not recommended for those whose symptoms are already severe, or who have the adult-onset or neonatal forms.
- Oral administration of docosahexaenoic acid (DHA) may help infants and children with neonatal ALD.
What is hyperlipoproteinaemia?
Disorders of lipoprotein metabolism and transport causing various hyperlipoproteinaemias, including:
- Familial hypercholesterolaemia
-Familial dysbetalipoproteinaemia - Familial chylomicronaemia
